Neonates born from human immunodeficiency virus (HIV)-infected mothers are currently identified as a high risk group in Western and Third World countries. It is the aim of this proposal to engineer antibody molecules that can be used for passive immunotherapy to prevent neonatal HIV infection. This project is based on a) the notion that the interaction between the CD4 receptor/molecule on T lymphocytes and HIV is a central feature in HIV infection, and b) a plausible prediction that interference with this interaction could guarantee protection. Protein engineering techniques will be used to construct antibodies that possess the HIV-binding domain of the CD4 receptor/molecule on immune cells, receptor (CD4)-like antibodies. This goal will be pursued by inserting discrete CD4 peptides from the putative HIV-binding site in the form of synthetic oligonucleotides into the immunoglobulin heavy- or light-chain gene, or both genes. These constructs will be expressed in mammalian cells by electroporation. The obtained CD4-like antibodies will be tested in vitro, immunochemically and biologically, for a) expression of the engineered HIV-binding domain, b) binding to HIV, and c) inhibition of viral infection of susceptible cells. The work proposed may constitute the basis for a new rational strategy to passive immunotherapy in the prevention of neonatal HIV infection and its consequences.